ABSTRACT
BACKGROUND/AIM: The relationship between the severity of cardioembolic stroke (CES) and oral anticoagulant (OAC) treatment before stroke onset in very elderly (≥80 years) patients with nonvalvular atrial fibrillation (NVAF) at high bleeding risk remains unknown. PATIENTS AND METHODS: A total of 364 consecutive patients (≥80 years) with CES and NVAF within 48 h following stroke onset were investigated. High bleeding risk was defined as follows: Bleeding history, renal dysfunction (creatinine clearance <30 ml/min), low body weight (≤45 kg), and antiplatelet or nonsteroidal anti-inflammatory drug use. Patients were divided into two groups: High bleeding risk (n=214) and non-high bleeding risk (n=150). We assessed stroke severity and functional outcome between the two groups, and evaluated the effect of therapy with direct OAC (DOAC) on stroke severity in the high-risk group. RESULTS: The high-risk group had a worse modified Rankin Scale (mRS) at discharge than the non-high-risk group [median: 4 (range=2-5) vs. 3 (range=1-4); p=0.02]. Patients in the high-risk group were categorized according to OAC treatment before stroke onset: No OAC (n=148), warfarin (n=46), and DOAC (n=20). The numbers of patients with National Institutes of Health Stroke Scale score (NIHSS) ≥8 on admission in these groups were 104 (70%), 30 (65%), and 8 (40%) (p=0.03), respectively. Multivariate analysis confirmed that DOAC therapy had a lower odds ratio (OR) for severe stroke (NIHSS ≥8) on admission (OR relative to no OAC=0.22, 95% confidence interval=0.08-0.62; p=0.005) and poor functional outcome (mRS ≥4) at discharge (OR=0.31, 95% confidence interval=0.11-0.90; p=0.03). CONCLUSION: Very elderly patients with CES at high bleeding risk have unfavorable functional outcomes. DOAC administration may be associated with reduced stroke severity.
Subject(s)
Atrial Fibrillation , Embolic Stroke , Stroke , Humans , Aged , Embolic Stroke/chemically induced , Embolic Stroke/complications , Embolic Stroke/drug therapy , Treatment Outcome , Risk Factors , Retrospective Studies , Anticoagulants/adverse effects , Hemorrhage/drug therapy , Hemorrhage/etiology , Stroke/diagnosis , Stroke/drug therapy , Stroke/etiology , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Administration, OralABSTRACT
BACKGROUND/AIM: The relationship between renal function and severity of cardioembolic stroke (CES) stratified by sex remains poorly understood. PATIENTS AND METHODS: A total of 640 consecutive CES patients within 48 h after stroke onset and with a modified Rankin Scale (mRS) score of 0 or 1 before onset were studied. The patients were divided into three groups based on their CCr values: low creatinine clearance (CCr) (L-CCr) (n=71, <30 ml/min), middle CCr (M-CCr) (n=227, 30 to <50 ml/min), and high CCr (H-CCr) (n=342, ≥50 ml/min). We compared the severity and functional outcomes of stroke among the three groups according to sex. RESULTS: On admission, using the National Institutes of Health Stroke Scale, the L-CCr group had the most severe stroke, followed by the M-CCr and H-CCr groups (p<0.0001). Functional outcomes at discharge, assessed using the mRS, were the worst in the L-CCr group, followed by the M-CCr and H-CCr groups (p<0.0001). Multivariable analyses revealed that L-CCr was a significant determinant of severe stroke on admission and poor functional outcomes at discharge. According to sex, L-CCr was a significant determinant of severe stroke on admission and poor functional outcomes at discharge in female patients, but not in male patients. CONCLUSION: Low CCr is a risk factor for severe stroke on admission and unfavorable functional outcomes at discharge in Japanese CES patients, and particularly in female patients.
Subject(s)
Atrial Fibrillation , Embolic Stroke , Stroke , Humans , Male , Female , Creatinine , Embolic Stroke/complications , East Asian People , Retrospective Studies , Stroke/diagnosis , Stroke/etiology , Risk FactorsABSTRACT
BACKGROUND: The INPULSIS trials revealed that nintedanib reduced the decline in lung function in patients with idiopathic pulmonary fibrosis. We aimed to evaluate the efficacy and safety of nintedanib in Japanese idiopathic pulmonary fibrosis patients in real-world settings. METHOD: Medical records of idiopathic pulmonary fibrosis patients, who received treatment with nintedanib in five institutions between July 2015 and June 2017, were reviewed. Patients with % forced vital capacity ⩾50% and % predicted diffusing capacity of the lung carbon monoxide ⩾30% were classified as the moderate group and those with more impaired lung functions as the severe group. RESULT: Among 158 patients analyzed, 132 (84.6%) were classified as the moderate group and 26 (15.4%) as the severe group. In the moderate group, changes in forced vital capacity in 12 months were significantly different between before and after nintedanib administration (-253 ± 163 vs -125 ± 235 mL; p = 0.0027). In contrast, changes in forced vital capacity in 12 months were not significantly changed by nintedanib treatment in the severe group (-353 ± 250 vs -112 ± 341 mL; p = 0.2374). Incidence of acute exacerbation was higher in the severe group than in the moderate group (30.8% vs 18.9%). The overall survival of the moderate and the severe groups was 17.2 and 10.1 months. CONCLUSION: In real-world practice, nintedanib showed comparable efficacy to those observed in previous trials. In the severe group, the efficacy of nintedanib might be limited.
ABSTRACT
OBJECTIVE: Procalcitonin (PCT) has received much attention as a serum marker for bacterial infection. Elevated serum PCT is occasionally seen in severe trauma, heatstroke, and neoplastic diseases, including lung cancer with neuroendocrine component. RESULTS: In the present study, we evaluated PCT expression in the specimen of pulmonary neuroendocrine tumors, comparing large cell neuroendocrine carcinoma (LCNEC), carcinoid, and small cell lung carcinoma (SCLC). Pathological specimens of 10 LCNEC, 4 carcinoid, and 7 SCLC cases were evaluated with immunochemical staining of PCT. Clinical characteristics and serum levels of PCT and C-reactive protein were also evaluated. We observed positive PCT expression in 5 (50%) LCNEC and 2 (50%) carcinoid specimens that were surgically resected. Whereas serum PCT levels were not elevated in patients with PCT-positive carcinoid, two out of three LCNEC patients with high PCT expression in the tumor had elevated serum PCT levels that reflected disease progression. In patients with SCLC, PCT was not detected in the tumor or serum. This is the first immunohistochemical study of the PCT expression in the lung tumor specimens. We concluded that, in patients with LCNEC, high serum PCT levels may be indicative of disease activity and serve as a biomarker.
Subject(s)
Carcinoma, Neuroendocrine , Carcinoma, Small Cell , Lung Neoplasms , Neuroendocrine Tumors , Carcinoma, Neuroendocrine/surgery , Humans , Lung , Neuroendocrine Tumors/surgery , ProcalcitoninABSTRACT
BACKGROUND: We examined cross-sectional associations between depression and both inflammatory markers and fractional exhaled nitric oxide (FeNO). METHODS: This cross-sectional study is a secondary analysis of the data of the Iwaki Health Promotion Project 2016 (1,148 subjects). We analyzed the subjects' characteristics and laboratory data including plasma interleukin (IL)-6, high-sensitivity C-reactive protein (hs-CRP), and FeNO. The subjects with Center for Epidemiologic Studies Depression Scale scores ≥16 were assigned to the depression group. We performed a multivariate logistic regression analysis to determine whether inflammatory markers and FeNO were associated with depression. RESULTS: We assessed 1,099 subjects (430 males, 669 females). The depression group was 237 subjects (21.5%) [84 males (19.5%), 153 females (22.9%)]. The non-depression group was 862 subjects (346 males and 516 females). There were no significant differences in IL-6, hs-CRP, or FeNO between both groups. However, the multivariate logistic regression analysis indicated that lower FeNO was significantly associated with depression in males after adjusting for possible confounding factors (age, BMI, comorbidities, high-sensitivity troponin T, FEV1%, asthma, antidepressant use, smoker and alcohol drinker) (per 1 bpm increase, OR: 0.982; 95%CI: 0.967-0.998; p = 0.032). CONCLUSION: Our findings indicate that lower FeNO may be associated with depression in males.
Subject(s)
Depression/blood , Exhalation/physiology , Inflammation Mediators/blood , Nitric Oxide/metabolism , Population Surveillance , Adult , Aged , Biomarkers/blood , Cross-Sectional Studies , Depression/diagnosis , Depression/epidemiology , Female , Forced Expiratory Volume/physiology , Humans , Japan/epidemiology , Male , Middle Aged , Nitric Oxide/analysisABSTRACT
Nintedanib has been approved for the treatment of idiopathic pulmonary fibrosis (IPF). In addition, in EU countries, nintedanib plus docetaxel is used for patients with advanced non-small cell lung cancer (NSCLC) after first-line chemotherapy. Here, we report a case of advanced NSCLC in a patient with IPF successfully treated with nintedanib monotherapy. A 69-year-old man was diagnosed with NSCLC complicated by IPF. After three lines of chemotherapy, he still had progressive disease. Because his IPF had also progressed, requiring supplemental oxygen, we decided to start best supportive care and introduced nintedanib to treat his IPF. One month later, we observed a partial remission of the primary tumor and pleural disseminations without severe adverse events. Nintedanib monotherapy might therefore be an effective therapeutic choice for NSCLC in patients with IPF who are unable to tolerate cytotoxic chemotherapy. KEY POINTS: Efficacy of nintedanib administered in a NSCLC patient with IPF. Nintedanib monotherapy might be a therapeutic option for NSCLC patients with IPF who are unable to tolerate chemotherapy.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Idiopathic Pulmonary Fibrosis/drug therapy , Indoles/therapeutic use , Lung Neoplasms/drug therapy , Aged , Carcinoma, Non-Small-Cell Lung/complications , Carcinoma, Non-Small-Cell Lung/pathology , Humans , Idiopathic Pulmonary Fibrosis/complications , Idiopathic Pulmonary Fibrosis/pathology , Lung Neoplasms/complications , Lung Neoplasms/pathology , Male , PrognosisABSTRACT
Afatinib, a second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) for mutant non-small cell lung cancer (NSCLC), was approved in Japan in 2014. This study evaluated clinical outcomes of afatinib in real-world practice. Medical records of patients who received afatinib for advanced EGFR-mutant NSCLC were retrospectively reviewed. In total, 128 patients were analyzed. Seventy-six patients received afatinib as the first-line setting and 52 as the re-challenge setting (i.e., after failure of prior first-generation TKI). There was no difference in patient characteristics, such as age, sex, and PS, between the first-line and the re-challenge settings. In the first-line setting, the median progression-free survival (PFS) was 17.8 months (95% confidence interval [CI] 13.7-21.5 months). The overall survival (OS) was 39.5 months (95% CI 34.4- not reached). The response rate (RR) was 64.4%. Subset analysis indicated that patients with dose reduction showed longer PFS than those without dose reduction (18.5 months versus 7.9 months) (P = 0.016). In the re-challenge setting, the median PFS was 8.0 months (95% CI 4.9-9.5 months). The RR was 25%. Most common adverse events leading to dose modification or treatment discontinuation included diarrhea, paronychia, and oral mucositis in both settings. Interstitial lung disease occurred in 5.4% (7/128). In the real-world practice in Japan, afatinib showed comparable or better efficacy compared with that shown in previous clinical trials in both the first-line and the re-challenge settings.
Subject(s)
Afatinib/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Adult , Afatinib/adverse effects , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Drug Resistance, Neoplasm , ErbB Receptors/genetics , Erlotinib Hydrochloride/pharmacology , Erlotinib Hydrochloride/therapeutic use , Female , Gefitinib/pharmacology , Gefitinib/therapeutic use , Humans , Japan , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Middle Aged , Mutation , Progression-Free Survival , Protein Kinase Inhibitors/adverse effects , Retrospective Studies , Survival Rate , Treatment OutcomeABSTRACT
The present retrospective study was conducted to evaluate the efficacy of immune checkpoint inhibitors (ICIs) in patients with advanced non-small cell lung cancer (NSCLC) harboring driver mutations. Patients with NSCLC harboring driver mutations who received ICIs (nivolumab or pembrolizumab) were reviewed in Hirosaki University and Aomori Prefectural Central Hospital. There were 139 patients who received molecular targeted drugs, including 24 patients treated with ICIs. Patient characteristics were as follows: Male/female, 5/19; median age 68 (range 39-82); smoking/non-smoking, 6/18; PS 0-1/2, 20/4; driver mutation status, EGFR/ALK/RET/ROS1: 21/1/1/1. The overall response rate was 16.7% [95% confidence interval (CI), 7.0-37.1%] and the disease control rate was 33.4% (95% CI, 18.9-55.1%). The median progression-free survival (PFS) time was 62 days (95% CI 52-81 days). In the patients who had been treated by the preceding tyrosine kinase inhibitor (TKI) for >1 year, the PFS time was 110 days. On the other hand, in the patients who had received a TKI for less than a year, the PFS time was 56 days, which was significantly shorter (P=0.012). To conclude, some of the patients with NSCLC harboring driver mutation could benefit from ICIs, and the duration of previous TKI treatment may be associated with the efficacy.
ABSTRACT
This phase I trial was conducted to determine the maximum tolerated dose (MTD) and recommended dose of afatinib for phase II trial in elderly patients with advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. The study used a standard 3 + 3 dose escalation design. Patients aged 75 years or older with advanced NSCLC harboring EGFR mutations were enrolled. The doses of afatinib, which were given once daily, were planned as follows: level 1, 20 mg/day; level 2, 30 mg/day; level 3, 40 mg/day. Dose-limiting toxicity (DLT) was defined as grade 4 hematologic, persistent grade > 2 diarrhea for > 2 days despite concomitant medications or grade 3 non-hematologic toxicity. DLT was evaluated during day 1-28. Fifteen patients were enrolled. Patient characteristics were: male/female 3/12; median age 79 (range 75-87); PS 0/1, 2/13. Six patients have been treated at levels 1 and 3, and three patients at level 2. At level 1, one of six patients experienced grade 3 rush, grade 3 anorexia, and grade 3 infection as DLTs. At level 2, none of three patients experienced a DLT. At level 3, two patients developed grade 3 diarrhea, one of whom also experienced grade 3 anorexia. Most frequent adverse events of any grade were diarrhea, paronychia, rush, and nausea. Most patients at level 2 and 3 required dose reduction in 3 months. MTD was defined as 40 mg/day, and recommended dose for phase II study in elderly patients was 30 mg/day.
Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , ErbB Receptors/genetics , Lung Neoplasms/drug therapy , Mutation , Quinazolines/therapeutic use , Afatinib , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Maximum Tolerated Dose , Prognosis , Survival RateABSTRACT
Sarcoidosis is an inflammatory granulomatous disease that is systemic, but bone involvement is uncommon. A 68-year-old man was referred to our hospital complaining of right shoulder pain with numbness. Computed tomography revealed systemic lymphadenopathy and multiple bone lesions. Because malignant lymphoma with a mass lesion protruding into the vertebral canal was considered, he underwent urgent radiotherapy. Thereafter, a needle biopsy of the left parasternal node was performed and showed epithelioid granulomas, confirming a diagnosis of sarcoidosis. Since his neurologic symptoms improved, the patient was not given systemic corticosteroids. Radiotherapy may be useful for local control of bone sarcoidosis.
Subject(s)
Sarcoidosis/complications , Spinal Cord Compression/etiology , Spinal Cord Compression/radiotherapy , Spinal Diseases/complications , Aged , Biopsy, Needle , Diagnosis, Differential , Humans , Lymphoma/diagnosis , Male , Mediastinum/pathology , Sarcoidosis/diagnostic imaging , Sarcoidosis/pathology , Spinal Diseases/diagnostic imaging , Spinal Diseases/pathology , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: We aimed to evaluate the efficacy and safety of nab-paclitaxel in patients with refractory advanced non-small cell lung cancer who failed previous chemotherapy. METHODS: Patients were required to have an Eastern Cooperative Oncology Group performance status of 0-2 and adequate organ function. Patients received nab-paclitaxel, 100 mg/m2 i.v. on days 1, 8, and 15 every 4 weeks. The primary endpoint was the overall response rate. Secondary endpoints were the progression-free survival time, overall survival, and the toxicity profile. RESULTS: From July 2013 to July 2015, a total of 31 patients were enrolled. Fourteen patients received nab-paclitaxel as a second-line and 17 received it as an over third-line therapy. Each patient received a median of 5 treatment cycles (range, 1-11). The overall response rate was 19.3% (95% confidence interval, 9.1-36.2%) (complete response (n = 0), partial response (n = 6), stable disease (n = 17), and progressive disease (n = 8)). The median progression-free survival time was 4.5 months (95% confidence interval 3.5-6.3 months), median overall survival time was 15.7 months, and 1-year survival rate was 54.8%. Most common grade 3 or 4 non-hematological toxicities were elevated aspartate transaminase level (3.2%) and sensory neuropathy (9.6%). Neutropenia was the most common grade 3 or 4 adverse events (38.6%), and febrile neutropenia developed in 12.9% patients. No treatment-related deaths were observed in this study. CONCLUSION: Primary endpoint was met. Single agent nab-paclitaxel showed significant clinical efficacy and manageable toxicities for patients with chemorefractory advanced non-small cell lung cancer even if late line setting. TRIAL REGISTRATION: UMIN000011696 . The date of registration was July 11th, 2013.
Subject(s)
Albumins/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Drug-Related Side Effects and Adverse Reactions/classification , Paclitaxel/administration & dosage , Aged , Aged, 80 and over , Albumins/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/pathology , Disease-Free Survival , Drug-Related Side Effects and Adverse Reactions/pathology , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Paclitaxel/adverse effectsABSTRACT
Crizotinib, which is effective in patients with anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer, is sometimes associated with the generation of complex renal cysts. A 56-year-old man with ALK positive adenocarcinoma received crizotinib. Ten months after the introduction of crizotinib, a cystic lesion developed from his right kidney to the iliopsoas muscle, accompanied by fever, anemia, and hypoproteinemia. After 17 months of treatment, crizotinib was switched to alectinib, followed by the recovery of hypoproteinemia and systemic inflammation. Switching to alectinib may be beneficial in patients demonstrating crizotinib-associated complex renal cysts with systemic inflammation and exhaustion.
Subject(s)
Adenocarcinoma/drug therapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Kidney Diseases, Cystic/chemically induced , Kidney Diseases, Cystic/drug therapy , Lung Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Pyrazoles/adverse effects , Pyridines/adverse effects , Receptor Protein-Tyrosine Kinases/therapeutic use , Antineoplastic Agents/therapeutic use , Carbazoles/therapeutic use , Carcinoma, Non-Small-Cell Lung/pathology , Crizotinib , Humans , Lung Neoplasms/pathology , Male , Middle Aged , Piperidines/therapeutic use , Pyrazoles/therapeutic use , Pyridines/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND: Lung cancers with anaplastic lymphoma kinase rearrangements are highly sensitive to anaplastic lymphoma kinase tyrosine kinase inhibition, underscoring the notion that such cancers are addicted to anaplastic lymphoma kinase activity. Several anaplastic lymphoma kinase inhibitors have been identified and are being evaluated in clinical trials. However patients with poor performance status (3 or 4) were not involved in these clinical trials, it has been unclear to use anaplastic lymphoma kinase-tyrosine kinase inhibitors for these patients. Here, we report an anaplastic lymphoma kinase-positive non small cell lung cancer patient with performance status 4, who was successfully treated with alectinib. CASE PRESENTATION: We report on a 52-year-old patient diagnosed as non small cell lung cancer harboring echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene. His performance status was 4 because of severe respiratory failure. We treated this patient with alectinib as the first line therapy. Dramatic response was obtained and his performance status improved from 4 to 1 without severe adverse events. CONCLUSION: Alectinib is a therapeutic option for the anaplastic lymphoma kinase positive patients with poor performance status.
Subject(s)
Carbazoles/therapeutic use , Gene Rearrangement/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Piperidines/therapeutic use , Receptor Protein-Tyrosine Kinases/genetics , Anaplastic Lymphoma Kinase , Bronchoscopy , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/drug therapy , Humans , Lung Neoplasms/diagnostic imaging , Male , Middle Aged , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
BACKGROUND: Listeria monocytogenes is a facultative intracellular parasitic bacterium that is Gram positive, catalase positive, oxidase negative, and a facultative anaerobe. It is known to infect humans through food. It is a bacillus with low virulence, but can cause meningitis and sepsis in infants and immunocompromised patients. CASE PRESENTATION: A case of 75-year-old Japanese female with small cell carcinoma of the thymus and pleural dissemination is described. She was treated with carboplatin and etoposide and showed a partial response. However, the tumor recurred 6 months later. Therefore, we again administered carboplatin and etoposide. Though peritoneal dissemination was suspected based on abdominal computed tomography findings after two courses, the assessment was stable disease. She was occasionally treated for constipation. She developed chills, rigor, and diarrhea, necessitating admission on the 7th day of the third course of chemotherapy. We suspected intestinal infection, and cefepime was thus administered. However, her blood pressure dropped and neutropenia manifested on the 4th day of admission. We therefore switched the antibiotic from cefepime to meropenem and also administered granulocyte-colony stimulating factor. Listeria monocytogenes was detected by two blood cultures, and the antimicrobial medication was thus switched to ampicillin, in consideration of sensitivity. Her general condition improved and she was able to leave the hospital on the 19th day after admission. CONCLUSIONS: During chemotherapy, factors such as impaired bowel movements, malnutrition, and myeloablation can contribute to the development of severe infections. It is necessary to comprehensively assess a patient's state and treat all aspects of illness.
Subject(s)
Antineoplastic Agents/adverse effects , Carboplatin/adverse effects , Carcinoma, Small Cell/drug therapy , Etoposide/adverse effects , Listeriosis/etiology , Neoplasm Recurrence, Local/drug therapy , Sepsis/etiology , Aged , Ampicillin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Antineoplastic Agents/administration & dosage , Carboplatin/administration & dosage , Carcinoma, Small Cell/pathology , Cefepime , Cephalosporins/therapeutic use , Etoposide/administration & dosage , Female , Granulocyte Colony-Stimulating Factor/therapeutic use , Humans , Listeria monocytogenes/drug effects , Listeria monocytogenes/pathogenicity , Listeria monocytogenes/physiology , Listeriosis/drug therapy , Listeriosis/microbiology , Listeriosis/pathology , Meropenem , Neoplasm Recurrence, Local/pathology , Sepsis/drug therapy , Sepsis/microbiology , Sepsis/pathology , Thienamycins/therapeutic use , Thymus Gland/drug effects , Thymus Gland/pathology , Thymus Neoplasms/drug therapy , Thymus Neoplasms/pathology , Treatment OutcomeABSTRACT
UNLABELLED: Immunohistochemical screening of Anaplastic lymphoma kinase (ALK) rearrangement has been regarded essential and routinely carried out to select treatment for lung adenocarcinoma. However, difficulty to approach a tumor by transbronchial lung biopsy (TBLB), it often fails to obtain tumor tissues whereas tumor cells are contained in cytology specimens simultaneously obtained when the bronchoscopy is done. Therefore we evaluated the expression of ALK protein by using immunohistochemistry (IHC) on TBLB specimens and immunocytochemistry (ICC) on brushing smear cytology slides in the same cases, and compared the concordance rate of IHC and ICC results. ICC was carried out on routine Papanicolau-stained slides after cytology diagnosis and decolorization. RESULTS: Eighteen patients with adenocarcinoma were extracted in the Hirosaki University Hospital and the Hirosaki National Hospital. IHC and ICC results showed a very high concordance rate: sensitivity of ICC in comparison with IHC was 85.7% (6/7), specificity was 100% (11/11), positive predictive value was 100% (6/6), and negative predictive value was 91.6% (11/12). Detection of ALK rearrangement using ICC on routine Papanicolau cytology slides is considered to be advantageous for lung cancer treatments.
Subject(s)
Adenocarcinoma/diagnosis , Cytodiagnosis , Lung Neoplasms/diagnosis , Receptor Protein-Tyrosine Kinases/genetics , Translocation, Genetic , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adenocarcinoma of Lung , Adult , Aged , Aged, 80 and over , Anaplastic Lymphoma Kinase , Bronchoscopy , Female , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Male , Middle AgedABSTRACT
BACKGROUND: Thymic carcinoma is a rare neoplasm of the thymus. Systemic chemotherapy is an important therapeutic modality for thymic carcinoma. However, no standard chemotherapy for this carcinoma has yet been established. The usefulness of second-line or later-line chemotherapy has remained unclear. A case of relapsed thymic carcinoma that was successfully treated by S-1 as second-line chemotherapy is reported herein. CASE PRESENTATION: A 73-year-old man diagnosed as having thymic carcinoma was treated with three cycles of first-line chemotherapy with ADOC (cisplatin, doxorubicin, vincristine, and cyclophosphamide) and additional radiotherapy (50 Gy). Since his serum cytokeratin 19 fragment level increased suddenly after 3 months of stable disease, he was considered to have progressive disease, and was given S-1 as chemotherapy. Two months later, he had partial response, and the S-1 treatment has been continued since July 2009. Progression-free survival of greater than 4 years was obtained with S-1. CONCLUSION: A case of relapsed thymic carcinoma that was treated with S-1, and continues to show a long progression-free survival with good quality of life on treatment is described. S-1 might be an active agent against relapsed thymic carcinoma.
ABSTRACT
BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide. Epidermal growth factor receptor (EGFR)--tyrosine kinase inhibitor (TKI) is used for the patients with EGFR-mutant lung cancer. Recently, phase III studies in the patients with EGFR-mutant demonstrated that EGFR-TKI monotherapy improved progression-free survival compared with platinum-doublet chemotherapy. The echinoderm microtubule-associated protein-like 4 (EML4)--anaplastic lymphoma kinase (ALK) fusion oncogene represents one of the newest molecular targets in non-small cell lung cancer (NSCLC). Patients who harbor EML4-ALK fusions have been associated with a lack of EGFR or KRAS mutations. CASE PRESENTATION: We report a 39-year-old patient diagnosed as adenocarcinoma harboring EGFR mutation and EML4-ALK fusion gene. We treated this patient with erlotinib as the third line therapy, but no clinical benefit was obtained. CONCLUSION: We experienced a rare case with EGFR mutation and EML4-ALK. Any clinical benefit using EGFR-TKI was not obtained in our case. The therapeutic choice for the patients with more than one driver mutations is unclear. We needs further understanding of the lung cancer molecular biology and the biomarker information.
Subject(s)
Adenocarcinoma/genetics , ErbB Receptors/genetics , Lung Neoplasms/genetics , Mutation , Oncogene Proteins, Fusion/genetics , Adenocarcinoma/diagnosis , Adenocarcinoma/therapy , Adult , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/therapy , MaleABSTRACT
The patient was a 36-year-old male. He visited our department in February 2004 as a prior chest X-ray revealed multiple nodular shadows. After further examinations, he was diagnosed with stage IV adenocarcinoma of the lung. As treatment, 5 courses of carboplatin (CBDCA)+docetaxel (DOC), 3 courses of CBDCA+gemcitabine (GEM), 6 weeks of gefitinib, and 3 courses of GEM were administered. However, the tumor progressed, and S-1 (120 mg/day, 2 weeks on, 1 week off) was administered as the sixth regimen from May 2006. No severe side effects were observed, and an antitumor action was achieved over a relatively long period. Therefore, it was suggested that a single administration of S-1 for non-small cell lung cancer, which had been treated with other multiple regimens, is safe, and long-term control of the disease can be expected.
Subject(s)
Adenocarcinoma/drug therapy , Antimetabolites, Antineoplastic/administration & dosage , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Oxonic Acid/administration & dosage , Tegafur/administration & dosage , Adult , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carboplatin/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Docetaxel , Drug Combinations , Gefitinib , Humans , Male , Quinazolines/administration & dosage , Taxoids/administration & dosage , GemcitabineABSTRACT
BACKGROUND: Bronchial asthma (BA) and allergic rhinitis (AR) are thought to share a common pathogenesis. However, reports concerning the comorbidity of the two diseases in a large-scaled population are rare in Japan. In the present study, we performed an analysis on the two diseases using questionnaires that addressed the diagnosis, symptoms and period of occurrence in more than 10,000 patients with BA or AR. METHODS: Patients with BA (adult: n = 2,781, childhood: n = 3,283) and AR (n = 3,945) were enrolled in the present study during the 3 months from August 1, 2006 to October 31, 2006. RESULTS: Sixty one percent of the patients with adult BA showed symptoms of AR. Among them, 68% of the patients were diagnosed with AR. Among the patients with childhood BA, 68% showed AR symptoms and 60% were diagnosed with AR. On the other hand, 49% of AR patients showed BA symptoms and 35% of them were diagnosed with BA. The symptoms of both BA and AR in the BA and AR patients were frequent in two seasons, March and April, and September and October. In addition, BA and AR symptoms often co-occurred in the patients with BA and AR. CONCLUSIONS: Comorbidity of BA and AR was high in both populations of BA and AR. The symptoms of both BA and AR co-occurred on both a daily and seasonal basis. These results suggested that BA and AR share a common immuno-pathogenesis in the airway and need to be treated as a single airway disease.
Subject(s)
Asthma/epidemiology , Rhinitis, Allergic, Perennial/epidemiology , Rhinitis, Allergic, Seasonal/epidemiology , Adult , Comorbidity , Humans , Seasons , Surveys and QuestionnairesABSTRACT
PURPOSE: Amrubicin, a new anthracycline agent, and topotecan are both active for previously treated small-cell lung cancer (SCLC). No comparative study of these agents has been reported. This randomized phase II study was conducted to select amrubicin or topotecan for future evaluation. PATIENTS AND METHODS: Patients with SCLC previously treated with platinum-containing chemotherapy were randomly assigned to receive amrubicin (40 mg/m(2) on days 1 through 3) or topotecan (1.0 mg/m(2) on days 1 through 5). Patients were stratified by Eastern Cooperative Oncology Group performance status (0, 1, or 2) and type of relapse (chemotherapy sensitive or refractory). The primary end point was overall response rate (ORR), and secondary end points were progression-free survival (PFS), overall survival, and toxicity profile. RESULTS: From February 2004 to July 2007, 60 patients were enrolled, and 59 patients (36 patients with sensitive and 23 patients with refractory relapse) were assessable for efficacy and safety evaluation. Neutropenia was severe, and one treatment-related death owing to infection was observed in the amrubicin arm. ORRs were 38% (95% CI, 20% to 56%) for the amrubicin arm and 13% (95% CI, 1% to 25%) for the topotecan arm. In sensitive relapse, ORRs were 53% for the amrubicin arm and 21% for the topotecan arm. In refractory relapse, ORRs were 17% for the amrubicin arm and 0% for the topotecan arm. Median PFS was 3.5 months for patients in the amrubicin arm and 2.2 months for patients in the topotecan arm. Multivariate analysis revealed that amrubicin has more influence than topotecan on overall survival. CONCLUSION: Amrubicin may be superior to topotecan with acceptable toxicity for previously treated patients with SCLC. Further evaluation of amrubicin for relapsed SCLC is warranted.